This document discusses drugs that act on the renin angiotensin system, including angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). It provides details on the mechanism of action, therapeutic uses and side effects of ACEIs such as Captopril, Enalapril, and Lisinopril. It also summarizes the mechanism of action, examples (Losartan, Valsartan), and uses of ARBs for conditions like high blood pressure and heart failure.

1. Drugs acting on Renin Angiotensin System
1. Angiotensin converting Enzyme Inhibitors (ACEI)
2. Angiotensin-II Receptor Blockers (ARBS)
1.ACE Inhibitors
Based on the Zn2+ binding groups
Sulphydral containing inhibitors: Captopril
Dicarboxylate containing inhibitors:
Enalapril, Lisinopril, Ramipril, Quinapril, Perindropril
Phosphate containing inhibitors: Fosinpril
Captopril & Lisinopril are non prodrugs
Remaining drugs are prodrugs

2. Captopril
-SH group enhance binding to Zn2+
In the ACE
The carboxylate ion (COO-) attract the
cationic site of the ACE by arginine residue, b/s of above
attachments, the carbonyl group becomes polarized
and more susceptible to hydrolysis instead of
angitensin-I
2-CH3 is important for action.
Substitution of other amino acid with proline
decrease the activity.

3. SAR
The N-ring must contain carboxylic acid
The N-ring should be large hydrophobic rings b/s it
increase the potency by altering pharmacokinetic
parameters

4. The A, B, C groups can serve as Zn2+ binding sites
The thiol group shows superior binding to Zn2+ among
the carboxylate and phosphate.
Estrification of carboxylate (B) and phosphate (C)
produces orally active products
 The X should be –CH3
In carboxylate derivatives X should be n- butylamine
The n usually 2 for activity

5. ACEI

6. Angiotensinogen
Angiotensin I
Angiotensin II
Renin
ACE
X
MOA OF ACEI
Aldoserone
Na reabsorption
Blood volume
Cardiac output
BP
ACEI
Aldoserone
Na reabsorption
Blood volume
Cardiac output
BP

7. Therapeutic Uses
Anti-hypertensive
Prevent or reverse LVH
Protect against sudden death and second
myocardial infarction after acute MI
Improve survival and hemodynamics in patients
with congestive heart failure
Protect against progression of diabetic
nephropathy

8. Adverse Effects
Hypotension
Renal Insufficiency (if bilateral renal artery
stenosis)
Hyperkalemia – special group of patients (Na
restricted, on K-sparing diuretic, COX inhibitors)
Cough (20 %)
Angioedema
With captopril especially: neutropenia, nephrotic
syndrome, skin rash, taste disturbances (SH
group- related).

9. 2. Angiotensin-II Receptor Blockers (ARBS)
Losartan
Valsartan
Telmisartan
Candesartan
Olmesartan

10. MOA
Angiotensin II receptor blockers (ARBs) act
differently from ACE inhibitors.
These drugs block the angiotensin-II binding to its
receptor,
Aldoserone production
Na reabsorption
Blood volume
Cardiac output
BP

11. Angiotensin II receptor
blockers can be used to
treat
coronary artery disease,
heart failure,
high blood pressure,
kidney disease.
Side effects
Chest pain
Back pain
Peripheral edema
Facial edema
Dry cough (less common)

12. Synthesis of Captopril